Attenuated, live virus vaccines are recognized as one of the most potent approaches to stimulating a protective immune response to pathogens and have been employed with success in the prevention of infectious diseases. Live virus vaccine vectors utilize the same advantages, stimulating both cytolytic T lymphocyte (CTL) activity and antibody production, without the danger of revertent virulent virus. Venezuelan equine encephalitis virus (VEE) derived vaccine vectors expressing heterologous genes have been developed with success in murine and primate models to protect against challenge with influenza virus (N. L. Davis et al., (1996) J. Virol. 70:3781-7), simian immunodeficiency virus (SIV; N. L. Davis et al., (1999) Proc. Natl. Acad. Sci. USA, submitted) and Marburg virus (M. Hevey et al., (1998) Virology 251:28-37).
In addition, live virus, non-propagating VEE replicon particles (VRP), expressing heterologous antigens, successfully protect against a lethal challenge of influenza in mice (P. Pushko et al., (1997) Virology 239:389-401) and SIV in primates (N. L. Davis et al., (1999) Proc. Natl. Acad. Sci. USA, submitted).
The goal of tumor immunotherapy is to induce a strong immune response against metastatic or residual disease. One of the most promising protocols in tumor immunotherapy is the use of ex vivo expanded dendritic cells (DC). Monocytes are isolated from peripheral blood then expanded and differentiated using cytokines and differential adhesion (reviewed in E. Gilboa et al., (1998) Cancer Immunol. Immunother, 46:82-7). These cells are modified via various protocols to present tumor antigens, and then the DC are infused back into the patient. DC are believed to target to the lymph nodes where they stimulate T cell immunity by interaction of the T cell receptor (TCR) of the T cell and class II and/or class I major histocompatability complex (MHC) of the DC.
These protocols, however, present several difficulties. First, large numbers of monocytes can be difficult to obtain from cancer patients due to an overall immunodepressed state. In addition, the ex vivo differentiation of the cells is time consuming and expensive and foreign proteins from the in vitro cultures can complicate the resulting immune response.
Given these drawbacks, there is a need in the art for alternative protocols for presenting tumor antigens in vivo to induce a host immune response thereto.